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MERTK on mononuclear phagocytes regulates T cell antigen recognition at autoimmune and tumor sites
Journal of Experimental Medicine ( IF 15.3 ) Pub Date : 2021-08-20 , DOI: 10.1084/jem.20200464
Robin S Lindsay 1, 2 , Jennifer C Whitesell 1, 2, 3 , Kristen E Dew 2 , Erika Rodriguez 2, 3 , Adam M Sandor 1, 2 , Dayna Tracy 2 , Seth F Yannacone 2 , Brittany N Basta 3 , Jordan Jacobelli 1, 2, 3 , Rachel S Friedman 1, 2, 3
Affiliation  

Understanding mechanisms of immune regulation is key to developing immunotherapies for autoimmunity and cancer. We examined the role of mononuclear phagocytes during peripheral T cell regulation in type 1 diabetes and melanoma. MERTK expression and activity in mononuclear phagocytes in the pancreatic islets promoted islet T cell regulation, resulting in reduced sensitivity of T cell scanning for cognate antigen in prediabetic islets. MERTK-dependent regulation led to reduced T cell activation and effector function at the disease site in islets and prevented rapid progression of type 1 diabetes. In human islets, MERTK-expressing cells were increased in remaining insulin-containing islets of type 1 diabetic patients, suggesting that MERTK protects islets from autoimmune destruction. MERTK also regulated T cell arrest in melanoma tumors. These data indicate that MERTK signaling in mononuclear phagocytes drives T cell regulation at inflammatory disease sites in peripheral tissues through a mechanism that reduces the sensitivity of scanning for antigen leading to reduced responsiveness to antigen.

中文翻译:

单核吞噬细胞上的 MERTK 调节自身免疫和肿瘤部位的 T 细胞抗原识别

了解免疫调节机制是开发针对自身免疫和癌症的免疫疗法的关键。我们检查了单核吞噬细胞在 1 型糖尿病和黑色素瘤中外周 T 细胞调节过程中的作用。MERTK 在胰岛单核吞噬细胞中的表达和活性促进了胰岛 T 细胞的调节,导致 T 细胞扫描对糖尿病前期胰岛中同源抗原的敏感性降低。MERTK 依赖性调节导致胰岛疾病部位的 T 细胞活化和效应功能降低,并阻止 1 型糖尿病的快速进展。在人类胰岛中,1 型糖尿病患者剩余的含胰岛素胰岛中表达 MERTK 的细胞增加,这表明 MERTK 保护胰岛免受自身免疫性破坏。MERTK 还调节黑色素瘤中的 T 细胞停滞。
更新日期:2021-08-21
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